Immaturity or Starvation? Longitudinal Study of Leptin Levels in Premature Infants

Objective: Leptin, the protein product of the ob gene, is a potential placental growth factor and is integral to the body’s system of energy regulation as shown in animal models. Premature infants are especially vulnerable to changes in energy regulation, and several studies have demonstrated a rapid fall in leptin values at birth. The purpose of the present investigation was to measure leptin levels in premature infants throughout hospitalization. Methods: Eligible infants were less than 32 weeks’ gestation, appropriate for gestational age, and hospitalized at Christiana Hospital Special Care Nursery. Serum samples for leptin analysis were drawn within 24 h of birth and twice a week thereafter until discharge. Concurrent growth measurements were obtained with each leptin sample. Body mass index, ponderal index, and midarm circumference/head circumference ratios were calculated to assess growth. Results: Leptin levels were low and remained low for the duration of the premature infants’ hospitalization (mean ± SD = 1.35 ± 0.63 ng/ml/ml, range 0–3.06). After controlling for weight, there was a small (r 2 = 0.1, p < 0.00001) but significant correlation between leptin and postnatal age after 4 days of age. Despite an increase in caloric intake during the study period, there was no relationship between leptin and caloric intake. There were significant negative correlations between measurements of growth and both leptin and the leptin/weight ratio. Maternal diabetes and the use of steroids had small but significant effects on the leptin/weight ratio. Conclusion: In this population of predominantly female premature infants, leptin levels were very low as compared to term infants, children and adults, and did not change appreciably over the study period. The low leptin levels seen in these premature infants are similar to those levels seen in malnourished adults, anorexics, and in animal models of starvation. We speculate that a critical adipose store needs to be reached before increased amounts of leptin can be adequately produced. Persistently low leptin levels may also reflect an immaturity in the hypothalamic-pituitary-adrenal axis.